At present, many kinds of nonsteroidal antiphlogistic analgesic agents having excellent anti-inflammatory, analgesic, and antipyretic actions, have been developed, and widely used against rheumatic disease, a postoperative pain or the pain after removal of a suture. Such a nonsteroidal antiphlogistic analgesic agent has been originally developed as an oral preparation, and has been employed as a useful therapeutic agent, however, the oral administration of such a nonsteroidal antiphlogistic analgesic agent may cause adverse effects such as gastrointestinal tract disorder etc.
On the other hand, an external preparation in the form of an ointment or a liquid drug has been developed for the treatment of arthrorheumatism, arthrosis deformans or low back pain, in order to change the administration route, so that the drug can be selectively delivered to the affected part, and the adverse effects caused from the oral administration, such as gastrointestinal tract disorder etc, can be alleviated. However, it is difficult to keep the applied dose or the applied area of these ointments and liquid drugs constant, and these ointments and liquid drugs often present a problem with use, i.e. the applied part becomes sticky, or these ointments and liquid drugs adhere to the clothes etc.
In contrast to this, patches are a preparation having the similar efficacy as those of the ointments and the liquid drugs. The patches are applied to a skin, and allow the drug to be transdermally absorbed into the body. The patches have various merits which are not owned by the ointments, such as accuracy of the applied dose, simplicity of the administration, and the hermeticity of the preparation applied to the affected part. In addition to these, the patches allow the drug to be continuously absorbed, thereby they show a prolonged action, therefore people has great expectations for the usefulness of the patches.
Presently, external skin patches containing three kinds of nonsteroidal agent (i.e. indomethacin, ketoprofen and flurbiprofen) have been on the market and their usefulness have been appreciated, as disclosed in the Japanese Unexamined Patent Application Publications No.2-212423, No.4-82828, No.8-319243, and No.9-124466.
At present, however, it is still difficult to provide analgesic effects against chronic pain coming from chronic arthrorheumatism, arthrosis deformans, low back pain and the like, even with these preparations. The reasons are believed to be as follows; the pain in the chronic arthrorheumatism, the arthrosis deformans and the low back pain are the somatic deep pain and the deep tissue causing such deep pain is not directly exposed to the external irritations, therefore the pain arises from fasciatonus or spasm caused by inflammation, patchion of nerve, nerve stimulus, bleeding, and edema etc. Either a local anesthetic or a nonsteroidal antiphlogistic analgesic agent when given alone for these symptoms does not work on both the inflammatory site and the peripheral nervous system, thereby the effect is limited. This is because, the local anesthetic reversibly anesthetizing a peripheral sensory nerve axis cylinder to lower or disappear the sensation of pain etc, and the nonsteroidal antiphlogistic analgesic agent working on a synapse on the path of pain, not on the sensory nerve fiber, to render the patient unaware of pain, have different mechanism of action on the pain respectively.
Accordingly, in the state of the art, a satisfactory external skin patch which has high painkilling effect for pains accompanied by inflammation, such as chronic arthrorheumatism, arthrosis deformans or low back pain, has not yet been developed.